Ever since the discovery of penicillin, numerous antibiotics have been developed by the pharmaceutical companies worldwide, including β-lactam antibiotics against bacterial infections, sulfonamides, tetracyclines, aminoglycosides, macrolides, quinolones, glycopeptides, and the like. And yet, new antibiotic resistant bacteria or multidrug resistant bacteria are incessantly occurring because of misuse or abuse of antibiotics. Due to this, concerns are increasing worldwide. The international microbiological community concerns that, with the evolution of antibiotic resistance, new resistant bacteria that are not affected by any currently used antibiotics might be rampant in near future.
In general, bacterial pathogens can be classified into Gram-positive or Gram-negative bacteria. In particular, Gram-positive bacteria, e.g. Staphylococcus, Enterococcus, Streptococcus and acid-fast bacteria, are very important. It is because, once occurring in a hospital environment, they are difficult to be eradicated and tend to develop into intractable resistant bacteria. Such resistant bacteria include methicillin-resistant Staphylococcus (MRSA), methicillin-resistant coagulase-negative Staphylococcus (MRCNS), penicillin-resistant Streptococcus pneumoniae, multiple-resistant Enterococcus faecium, or the like.
For the clinically effective treatment of the Gram-positive bacteria, vanomycin, a glycopeptide antibiotic, is often used. However, vancomycin is related with a variety of toxicities and, since the emergence of vancomycin-resistant Enterococcus (VRE) in 1990s, bacteria resistant to vancomycin and other glycopeptide-based antibiotics are emerging.
And, for antibiotics such as β-lactam, quinolone and macrolide used to treat infections of the upper respiratory tract caused by specific Gram-negative bacteria including Haemophilus influenzae (H. influenzae) and Moraxella catarrhalis (M. catarrhalis), resistant bacteria like quinoline-resistant Staphylococcus aureus (QRSA) are emerging. Hence, researches on new antibiotics are under way.
Accordingly, in order to fundamentally solve the antibiotic resistance problem, development of antibiotics with new chemical structure and antibacterial mechanism is urgent. In this respect, since an oxazolidinone antibiotic with a new chemical structure was first reported in 1984 by DuPont (European Paten Publication No. 127,902), a variety of oxazolidinone derivatives have been designed and synthesized by many pharmaceutical companies.
Those oxazolidinone derivatives are new synthetic antibiotics and might be administered orally. The oxazolidinone antibiotics have a totally different chemical backbone from the classical antibiotics. Since they inhibit the initial stage of protein synthesis, they exhibit superior antibacterial activity against antibiotic-resistant bacteria, particularly Gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), quinolone-resistant Staphylococcus aureus (QRSA), vancomycin-resistant Enterococcus (VRE) and multidrug-resistant Mycobacterium tuberculosis (MDRTB).
As examples of oxazolidinone compounds including an oxazolidinone ring, 3-phenyl-2-oxazolidinone derivatives having one or two substituent(s) are described in U.S. Pat. Nos. 4,948,801, 4,461,773, 4,340,606, 4,476,136, 4,250,318 and 4,128,654, and 3-[(mono-substituted)phenyl]-2-oxazolidinone derivatives represented by Chemical Formula A are described in EP 0312000, J. Med. Chem. 32, 1673(1989), J. Med. Chem. 33, 2569 (1990), Tetrahedron Lett. 45,123(1989), and the like.

And, oxazolidinone derivatives represented by Chemical Formula B and Chemical Formula C were synthesized by Pharmacia & Upjohn (WO 93/23384, WO 95/14684 and WO 95/07271). The compound of Chemical Formula B, “linezolid”, is the first oxazolidinone antibiotic and is marketed under the trade name “zyvox” for oral administration and injection, approved by the U.S. Food and Drug Administration (FDA). However, most of synthetic oxazolidinone compounds are associated with some limitations, such as toxicity, low in vivo efficacy and low solubility. As for linezolid, solubility in water is only about 3 mg/mL, which causes its use as injection limited.

WO 93/09103 discloses phenyl oxazolidinone derivatives having a heterocyclic ring, including pyridine, thiazole, indole, oxazole, quinol, etc., at the 4-position of the phenyl group. But, the substituents of the heterocyclic ring are merely simple alkyl or amino group, and the activities are not so excellent.
In order to solve these problems, WO 01/94342 discloses phenyloxazolidinone derivatives having various pyridine or phenyl derivatives at the 4-position of the phenyl group. The synthetic compounds have wide antibacterial spectrum and excellent antibacterial activity. Although the oxazolidinone compounds having various pyridine derivatives at the 4-position of the phenyl group of oxazolidinone have wider antibacterial spectrum and excellent antibacterial activity as compared to linezolid, most of them have aqueous solubility of 30 μg/mL or less, and thus have limitation in preparing injections.
TR-700 and TR-701, represented by Chemical Formula D, are developed by Dong-A Pharmaceutical and recently licensed to Trius Therapeutics. TR-701 is a prodrug of TR-700 and it is in the phase II clinical trial. TR-701 solves the solubility problem via formation of prodrug from TR-700, exhibits an antibacterial activity superior to that of linezolid. However, the compound shows higher toxicities (cytotoxicity, MAO profile, myelosuppression, etc.) than linezolid, and, thus, is expected to have many limitations.

As described above, a compound having superior antibacterial activity, satisfactory solubility and lower toxicity is yet to be found.